Lim domain binding 2: a key driver of transendothelial migration of leukocytes and atherosclerosis.

Autor:	Shang MM; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Talukdar HA; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Hofmann JJ; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Niaudet C; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Asl HF; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Jain RK; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Rossignoli A; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Cedergren C; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Silveira A; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Gigante B; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Leander K; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., de Faire U; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Hamsten A; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Ruusalepp A; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Melander O; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Ivert T; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Michoel T; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Schadt EE; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Betsholtz C; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Skogsberg J; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.)., Björkegren JL; From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.). johan.bjorkegren@ki.se.
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2014 Sep; Vol. 34 (9), pp. 2068-77. Date of Electronic Publication: 2014 Jun 12.
DOI:	10.1161/ATVBAHA.113.302709
Abstrakt:	Objective: Using a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis. Approach and Results: mRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100) mice, loss of Ldb2 increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was associated with the risk and extent of CAD across several cohorts. Conclusions: As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML. (© 2014 American Heart Association, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu